Novel Inhibitor Design for Hemagglutinin against H1N1 Influenza Virus by Core Hopping Method

Li, Xiao-Bo; Wang, Shu-Qing; Xu, Wei-Ren; Wang, Run-Ling; Chou, Kuo-Chen

The Glide5 docking program [39] interfaced with Schrodinger Suite 2009 [33] was used to screen the drug-like database from ZINC [38] based on the 3D structure of 3AL4. The preparation and refinement protocols for protein receptor and all compound structures were performed on the Protein Preparation Wizard and LigPrep modules embedded in Schrodinger 2009 [33] , respectively. For protein preparation, the process included assigning bond orders, adding hydrogen, treating metals, treating disulfides, deleting waters and alleviating potential steric clashes, adjusting bond order and formal charges by protein minimization with the OPLS2005 force field [40] , the constrained refinement value of RMSD for the protein was limited to 0.3 Ã… . Meanwhile, for the compounds, the preparation consisted of the generating possible states by ionization at target pH 7.062.0, desalting, retaining chiralities from 3D structure and geometry minimization with the OPLS2005 force field [40] . When the above steps were accomplished, all investigated compounds were docked into the receptor pocket through the rigid docking model with the Standprecision (SP) scoring function [41, 42] to estimate the binding affinities.